We are studying the interactions between poliovirus and its host cell which result in selective interference with protein synthesis directed by cellular messenger RNA. Infection of cells with poliovirus results in a rapid inhibition of cellular protein synthesis, followed by efficient translation of only viral mRNA. The untranslated cellular mRNA remains structurally and functionally intact, but its translation is blocked at the step of initiation complex formation. Preparations of initiation factors from infected cells show a mRNA-discriminatory activity which results in the failure of infected cell initiation factors to function in the synthesis of host cell proteins, although this preparation is active for stimulating synthesis of viral proteins. The activity of eIF3 appears to be defective in infected cells, and an additional, unidentified component has been resolved which functions in the initiation process. The initiation of viral protein synthesis has been examined in vitro, and has been shown to occur at two different initiation sites on the viral mRNA. We are examining both cellular and viral protein synthesis in an effort to biochemically define each process and to understand the mechanism by which selectivity for different mRNA populations can be imposed.